Study maps key stages of immune response to deadly fungal infection

Building on earlier breakthroughs, Kirsten Nielsen's laboratory in the Virginia-Maryland College of Veterinary Medicine has unveiled the body's step-by-step battle against Cryptococcus neoformans, a potentially deadly fungal infection.

The Nielsen lab’s latest research as part of the Center for One Health Research at Virginia Tech reveals a precise timeline of immune responses that could reshape treatment strategies. The research was recently published in mBio, the premier journal of the American Society for Microbiology.

The research addresses a critical challenge: understanding how this potentially fatal fungal infection develops and spreads.  

Think of Cryptococcus neoformans as an unwanted guest that can either stay quietly in your lungs or cause chaos if it reaches your brain. The body's security system – specialized structures called granulomas – tries to keep this fungal intruder contained. But until now, scientists weren't sure how these protective granuloma barriers formed or functioned.

"While our previous work focused on identifying the genetic factors that influence disease severity in susceptible people, this new research helps us understand exactly how the body controls Cryptococcus infections over time in healthy people," said Nielsen, professor of microbiology and immunology in the Department of Biomedical Sciences and Pathobiology. "We've essentially created a timeline of how the immune system contains the infection."

The study identified three distinct chapters in the body's defense story:

• First, non-specific inflammatory cells rush in while the fungus attempts to gain ground. 
• Next, specialized immune cells build the protective granuloma structures.
• Finally, T-cells arrive in force, often successfully containing the infection.

This detailed understanding of the immune response timeline could have significant implications for treatment strategies. By knowing which immune responses are most effective at controlling the infection and preventing disease, physicians can better time and target treatments to use the body's natural defense mechanisms.

The findings complement the laboratory's recent work on Cryptococcus genetics, published in Nature Communications, which identified genes associated with disease severity. Together, these studies are building a comprehensive picture of both how the pathogen causes disease and how the body fights back.

"Each piece of research brings us closer to our ultimate goal of preventing and better treating these infections," Nielsen said. "Understanding both the pathogen's genetics and the host's immune response gives us a much more complete picture of how to fight this disease."

The Center for One Health Research is a collaboration between the veterinary college, located at Virginia Tech, and the Edward Via College of Osteopathic Medicine. The research demonstrates the center's commitment to One Health, the philosophy that human, animal, and environmental health are inextricably linked.